Total Synthesis of (±)-Fasicularin through Double Consecutive Epimerizations.

Area of Science:

• Organic Chemistry
• Natural Product Synthesis
• Medicinal Chemistry

Background:

• Marine alkaloids, such as fasicularin, are complex molecules with potential biological activities.
• Developing efficient synthetic routes to these compounds is crucial for further study and potential applications.

Purpose of the Study:

• To achieve the total synthesis of the tricyclic marine alkaloid fasicularin.
• To develop a novel and efficient synthetic strategy for complex alkaloid structures.

Main Methods:

• Total synthesis of fasicularin starting from a novel α-aminonitrile.
• Utilized a novel double consecutive epimerization process.
• Employed iridium-catalyzed reductive functionalization of a tertiary γ-lactam.

Main Results:

• Successfully synthesized tricyclic marine alkaloid fasicularin (1b).
• Achieved the required stereochemical configuration through thermodynamically driven isomerization.
• Demonstrated an efficient route from affordable starting materials.

Conclusions:

• The developed strategy provides an efficient pathway to fasicularin and related tricyclic structures.
• The novel synthetic methodologies, including double epimerization and Ir-catalyzed functionalization, are valuable for complex molecule synthesis.